Quantitative and site-specific chemoproteomic profiling of O-GlcNAcylation in Drosophila

IF 3.3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic & Medicinal Chemistry Pub Date : 2025-04-10 DOI:10.1016/j.bmc.2025.118191

Cong Lei , Zihan Chen , Yi Hao , Wanping Huang , Tianyu Chu , Kangming Xiao , Che Zhang , Wen Zhou , Chenjian Li , Xing Chen

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引用次数: 0

Abstract

Protein O-GlcNAcylation plays a crucial role in Drosophila melanogaster development. Dysregulation of O-GlcNAc transferase (sxc/Ogt) and O-GlcNAcase (Oga) disrupts early embryogenesis and locomotor behavior. It is therefore of great interest to identify and quantitatively analyze O-GlcNAcylation sites in Drosophila. Here, we perform quantitative and site-specific profiling of O-GlcNAcylation in Drosophila by employing a chemoenzymatic labeling strategy. A total of 2196 unambiguous O-GlcNAcylation sites and 1308 O-GlcNAcylated proteins are identified. Quantitative analysis of O-GlcNAcylation in the head of Drosophila with sxc/Ogt knockdown in GABAergic neurons reveals a reduction in O-GlcNAcylation of several proteins involved in muscle development, consistent with the phenotypic defects observed in sxc/Ogt RNAi Drosophila. Furthermore, quantitative analysis of O-GlcNAcylation under a high-sugar diet reveals altered O-GlcNAcylation of several proteins associated with obesity and neurological diseases, such as Hex-A and Ankyrin 2. Our study not only establishes an effective method for large-scale identification of O-GlcNAcylation sites, but also provides a valuable resource for studying O-GlcNAc biology in Drosophila.

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果蝇o - glcn酰化的定量和位点特异性化学蛋白质组学分析

蛋白o - glcn酰化在果蝇发育中起着至关重要的作用。o - glcnnac转移酶（sxc/Ogt）和O-GlcNAcase （Oga）的失调会破坏早期胚胎发生和运动行为。因此，鉴定和定量分析果蝇的o - glcn酰化位点具有很大的兴趣。在这里，我们通过采用化学酶标记策略对果蝇的o - glcn酰化进行定量和位点特异性分析。共鉴定出2196个明确的o - glcn酰化位点和1308个o - glcn酰化蛋白。对gaba能神经元中sxc/Ogt敲低的果蝇头部o - glcn酰化的定量分析显示，参与肌肉发育的几种蛋白质的o - glcn酰化减少，这与在sxc/Ogt RNAi果蝇中观察到的表型缺陷一致。此外，高糖饮食下o - glcn酰化的定量分析显示，与肥胖和神经系统疾病相关的几种蛋白质（如Hex-A和锚蛋白2）的o - glcn酰化发生了改变。我们的研究不仅建立了大规模鉴定o - glcn酰化位点的有效方法，而且为研究果蝇o - glcnnac生物学提供了宝贵的资源。

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来源期刊

Bioorganic & Medicinal Chemistry 医学-生化与分子生物学

CiteScore

6.80

自引率

2.90%

发文量

413

审稿时长

17 days

期刊介绍： Bioorganic & Medicinal Chemistry provides an international forum for the publication of full original research papers and critical reviews on molecular interactions in key biological targets such as receptors, channels, enzymes, nucleotides, lipids and saccharides. The aim of the journal is to promote a better understanding at the molecular level of life processes, and living organisms, as well as the interaction of these with chemical agents. A special feature will be that colour illustrations will be reproduced at no charge to the author, provided that the Editor agrees that colour is essential to the information content of the illustration in question.